6568 J . Org. Chem., Vol. 61, No. 19, 1996
Ono et al.
N -(1,1,1-Tr iflu or o-3-b r om oisop r op ylid e n e )b e n zyl-
a m in e (2k ): 28.9%, Rf 0.23. 1H NMR δ 4.00 (s, 2H), 4.83 (m,
2H), 7.38-7.39 (m, 5H); 19F NMR δ -72.56 (s); MS m/z 279,
281 (M, 2.3, 2.1), 91 (100).
7.71-7.74 (m, 2H), 8.40 (m, 1H); 19F NMR δ -143.79 (m, 2F),
-155.81 (m, 1F), -162.75 (m, 2F); MS m/z 285 (M, 72), 284
(M - H, 46), 181 (100). Anal. Calcd for C14H8F5N: C, 58.96;
H, 2.83; N, 4.91; F, 33.31. Found: C, 59.05; H, 2.74; N, 4.87;
F, 33.25.
N-Ben zylid en e-1,1,1-tr iflu or oisop r op yla m in e (5i):8a Rf
0.41; 1H NMR δ 1.44 (d, 3H, J H-H ) 6.6 Hz), 3.84 (septet, 1H,
J H-H ) J H-F ) 6.6 Hz), 7.42-7.46 (m, 3H), 7.77-7.80 (m, 2H),
8.33 (m, 1H); 19F NMR δ -76.86 (d, J H-F ) 6.6 Hz); 13C NMR
δ 15.95 (q, J C-F ) 2.0 Hz), 66.80 (q, J C-F ) 28.4 Hz), 125.76
(q, J C-F ) 279.7 Hz), 128.74, 128.78, 131.62, 135.45, 164.60;
MS m/z 201 (M, 38), 200 (M - H, 9), 186 (M - CH3, 4), 132 (M
- CF3, 100).
N -(1,1,1-Tr iflu or o-3-p h e n ylisop r op ylid e n e )b e n zyl-
a m in e (2l) (in a 1.3/1 mixture with corresponding enamine):
89.5%, Rf 0.31; 1H NMR δ 3.92 (s, 1.12H), 4.69 (s, 1.12H,
ketimine), 3.65 (br s, 0.44H), 4.06 (d, 0.88H, J H-H ) 4.5 Hz),
6.10 (s, 0.44H, enamine), 7.16-7.35 (m, 10H); 19F NMR δ
-68.61 (s, enamine), -72.94 (s, ketimine); MS m/z 277 (M, 16),
91 (100). Anal. Calcd for C16H14F3N: C, 69.30; H, 5.09; N,
5.05; F, 20.56. Found: C, 69.44; H, 5.17; N, 5.07; F, 20.34.
N -(1-P h e n yl-2,2,2-t r iflu or oe t h ylid e n e )b e n zyla m in e
1
(2m ):8a 67%, Rf 0.35; H NMR δ 4.61 (s, 2H), 7.26-7.31 (m,
N -B e n z y l i d e n e -5 ,5 ,5 ,4 ,4 ,3 ,3 -h e p t a fl u o r o p e n t -2 -
yla m in e (5j): Rf 0.30; 1H NMR δ 1.46 (d, 3H, J H-H ) 6.6 Hz),
4.03 (m, 1H), 7.43-7.47 (m, 3H), 7.76-7.79 (m, 2H), 8.32 (s,
1H); 19F NMR δ -81.32 (t, 3F, J F-F ) 10.2 Hz), -119.19,
-124.15 (ABX, 2F, J AB ) 278.9 Hz, J AX ) 10.2 Hz), -124.71,
-126.52 (ABXY, 2F, J AB ) 291.0 Hz, J AX ) 14.4 Hz, J AY ) 7.1
Hz, J BX ) 12.1 Hz); MS m/z 301 (M, 5), 132 (M - C3F7, 100).
N-Ben zylid en e-3,3,3-tr iflu or op r op en -2-yla m in e (8): Rf
10H); 19F NMR δ -71.41 (s); MS m/z 263 (M, 19), 91 (100).
N-(1-P h en yl-2-ch lor o-2,2-d iflu or oet h ylid en e)b en zyl-
a m in e (2n ): 27%, Rf 0.38; 1H NMR δ 4.56 (s, 2H), 7.25-7.37
(m, 10H); 19F NMR δ -61.35 (s, 1F), -58.54 (s, 1F); MS m/z
279 (M, 1), 244 (M - Cl, 3), 91 (100).
Gen er a l Meth od of Isom er iza tion of 2a -n to N-Ben -
zylid en e Der iva tives 5a ,b,d -j,l-n a n d 6-9. The starting
compound 2a -n (typically 25-30 mmol) was dissolved in 3-5
mL of TEA, and the mixture was stirred at the temperature
and for the time indicated in Table 1. Progress of the
isomerization was monitored by NMR or GLC, and upon
completion, any undissolved solid was removed by filtration
and TEA was evaporated in vacuo. The residual material was
dried via an oil pump to completely remove the TEA or purified
by column chromatography to give products listed below.
Yields are given in Table 1.
1
0.25; H NMR δ 5.11 (m, 1H), 5.24 (br s, 1H), 7.48-7.52 (m,
3H), 7.87 (m, 2H), 8.42 (s, 1H); 19F NMR δ -70.25 (s); MS m/z
199 (M, 65), 198 (M - H, 30), 130 (M - CF3, 87), 103 (100).
N -B e n zy lid e n e -1,1,1-t r iflu o r o -3-p h e n y lis o p r o p y l-
1
a m in e (5l): Rf 0.39; H NMR δ 3.06, 3.26 (ABX, 2H, J AB
)
)
13.2 Hz, J AX ) 2.1 Hz, J BX ) 10.8 Hz), 3.78 (dqd, 1H, J H-H
10.8 Hz, J H-F ) 7.1 Hz, J H-H ) 2.1 Hz), 7.09-7.65 (m, 10H),
7.66 (s, 1H); 19F NMR δ -75.36 (d, J H-F ) 7.1 Hz); MS m/z
277 (M, 24), 186 (M - PhCH2, 100). Anal. Calcd for
C16H14F3N: C, 69.30; H, 5.09; N, 5.05; F, 20.56. Found: C,
69.39; H, 5.03; N, 5.11; F, 20.47.
N-Ben zylid en e-2,2,2-tr iflu or oeth yla m in e (5a ): Rf 0.35;
1H NMR δ 4.12 (q, 2H, J H-F ) 9.3 Hz), 7.41-7.48 (m, 3H),
7.77-7.81 (m, 2H), 8.35 (s, 1H); 19F NMR δ -71.42 (t, J H-F
)
N-Ben zyliden e-1-ph en yl-2,2,2-tr iflu or oeth ylam in e (5m ):
Rf 0.32; H NMR δ 4.80 (q, 1H, J H-F ) 7.5 Hz), 7.37-7.47
9.3 Hz); MS m/z 187 (M, 61), 186 (M - H, 26), 118 (M - CF3,
66), 91 (100). Anal. Calcd for C9H8F3N: C, 57.76; H, 4.31; N,
7.49; F, 30,45. Found: C, 57.64; H, 4.33; N, 7.51; F, 30.40.
N-Ben zylid en e-2-ch lor o-2,2-d iflu or oet h yla m in e (5b )
a n d N-Ben zylid en e-2,2-d iflu or ovin yla m in e (6) (1:1 Mix-
tu r e). For compound 5b: 1H NMR δ 4.25 (t, 2H, J H-F ) 11.1
Hz), 7.35-7.43 (m, 3H), 7.77-7.81 (m, 2H), 8.35 (s, 1H); 19F
NMR δ -57.78 (t, J H-F ) 11.1 Hz); GS-MS m/z 203, 205 (M,
4.8, 1.5), 91 (100). For compound 6: 1H NMR δ 6.13 (d, 1H,
J H-F ) 17.0 Hz), 7.35-7.43 (m, 3H), 7.77-7.81 (m, 2H), 8.17
8a
1
(m, 6H), 7.54-7.58 (m, 2H), 7.82-7.85 (m, 2H), 8.38 (s, 1H);
19F NMR δ -74.39 (d, J H-F ) 7.5 Hz); 13C NMR [H,F decouple]
δ 75.23, 124.64, 128.69, 128.78, 128.92 (2 C), 129.02, 131.77,
135.13, 135.49, 165.89; MS m/z 263 (M, 20), 194 (M - CF3,
100).
N-Ben zylid en e-1-p h en yl-2-ch lor o-2,2-d iflu or oet h yl-
a m in e (5n ): Rf 0.35; 1H NMR δ 4.88 (dd, 1H, J H-F ) 8.5, 10.5
Hz), 7.39-7.51 (m, 6H), 7.59-7.61 (m, 2H), 7.86-7.90 (m, 2H),
8.42 (s, 1H); 19F NMR δ -59.47, -61.00 (ABX, J AB ) 162.0
Hz, J AX ) 8.5 Hz, J BX ) 10.5 Hz); MS m/z 279 (M, 1), 244 (M
- Cl, 2), 194 (100).
(s, 1H); 19F NMR δ -85.77 (dd, 1F, J F-F ) 24.0 Hz, J H-F
)
17.0 Hz), -98.73 (d, 1F, J F-F ) 24.0 Hz); MS m/z 167 (M, 84),
166 (M - H, 29), 140 (100), 117 (22), 90 (98), 89 (72), 77 (55),
63 (39).
N-Ben zylid en e-1-p h en yl-2,2-d iflu or ovin yla m in e (9): Rf
1
0.31; H NMR δ 7.37-7.50 (m, 10H), 8.01 (s, 1H); 19F NMR δ
N-Ben zylid en e-2,2-d ich lor ovin yla m in e (7): Rf 0.35, mp
-91.27 (d, 1F, J F-F ) 22.3 Hz), -95.27 (d, 1F, J F-F ) 22.3
Hz); MS m/z 243 (M, 27), 140 (100).
1
50-52 °C; H NMR δ 7.20 (s, 1H), 7.42-7.47 (m, 3H), 7.83-
7.86 (m, 2H), 8.26 (s, 1H); 13C NMR δ 123.25 (s), 128.92 (s),
129.19 (s), 132.06 (s), 135.71 (s), 139.73 (s), 162.40 (s); MS m/z
199, 201, 203 (M, 94.5, 57.3, 8.4), 164 (100).
Gen er a l Meth od of Hyd r olysis of N-Ben zylid en e De-
r iva tives 5d ,e,h ,i,l,m to Hyd r och lor id es 10d ,e,h ,i,l,m . The
starting Schiff base 5d ,e,h ,i,l,m (typically 20 mmol) was
dissolved in 5 mL of ether, and 5 mL of 4 N HCl was added
under stirring at ambient temperature. Progress of the
hydrolysis was monitored by TLC, and upon completion, the
aqueous layer was separated, washed with ether, and evapo-
rated in vacuo to give crystalline hydrochloride 10d ,e,h ,i,l,m ,
purified by recrystallization from acetone or acetonitrile.
Hydrochlorides 10d ,e,h ,i,l,m give no definite melting points
but easily sublimate over 180 °C.
1,1-Dih ydr oper flu or obu tylam in e h ydr och lor ide (10d):
96% from N-benzylidene derivative 5d ; 1H NMR (CD3CN/CD3-
OD, 3:1) δ 4.83 (tt, J H-F ) 16.7, J H-F ) 1.2 Hz); 19F NMR (CD3-
CN/CD3OD, 3:1) δ -80.24 (t, 3F, J F-F ) 8.5 Hz), -117.49 (m,
2F), -127.138 (d, 2F, J H-F ) 1.2 Hz).
N -Be n zylid e n e -4,4,4,3,3,2,2-h e p t a flu or ob u t yla m in e
1
(5d ): Rf 0.38; H NMR δ 4.20 (t, 2H, J H-F ) 15.6 Hz), 7.43-
7.48 (m, 3H), 7.77-7.80 (m, 2H), 8.36 (s, 1H); 19F NMR δ
-81.22 (t, 3F, J F-F ) 8.5 Hz), -118.06 (m, 2F), -127.66 (br s,
2F). Anal. Calcd for C11H8F7N: C, 46.01; H, 2.81; N, 4.88; F,
46.31. Found: C, 46.17; H, 2.87; N, 4.73; F, 46.26.
N -B e n zy lid e n e -5,5,5,4,4,3,3,2,2-n o n a flu o r o p e n t y l-
a m in e (5e):8a Rf 0.39; 1H NMR δ 4.20 (t, 2H, J H-F ) 15.8 Hz),
7.44-7.49 (m, 3H), 7.75-7.79 (m, 2H), 8.32 (s, 1H).
N-Ben zylid en e-5,5,4,4,3,3,2,2-oct a flu or op en t yla m in e
(5f): Rf 0.35; 1H NMR δ 4.23 (t, 2H, J H-F ) 15.6 Hz), 6.10 (tt,
1H, J H-F ) 52.0, 5.4 Hz), 7.42-7.49 (m, 3H), 7.76-7.80 (m,
2H), 8.35 (s, 1H). Anal. Calcd for C12H9F8N: C, 45.15; H, 2.84;
N, 4.39; F, 47.62. Found: C, 45.21; H, 2.87; N, 4.27; F, 47.58.
N -Be n zylid e n e -7,7,6,6,5,5,4,4,3,3,2,2-d od e ca flu or o-
1,1-Dih ydr oper flu or open tylam in e h ydr och lor ide (10e):
91% from N-benzylidene derivative 5e; H NMR (CD3CN/
8a
1
h ep tyla m in e (5g): Rf 0.35; 1H NMR δ 4.21 (t, 2H, J H-F
)
CD3OD, 3:1) δ 4.87 (tt, J H-F ) 16.9, J H-F ) 1.2 Hz).
15.3 Hz), 6.05 (tt, 1H, J H-F ) 51.6, 5.4 Hz), 7.40-7.49 (m, 3H),
7.77-7.80 (m, 2H), 8.36 (s, 1H); 19F NMR δ -117.11 (m, 2F),
-122.49 (br s, 2F), -123.35 (br s, 2F), -124.02 (br s, 2F),
-130.11 (m, 2F), -137.51 (d, J H-F ) 51.6 Hz). Anal. Calcd
for C14H9F12N: C, 40.11; H, 2.16; N, 3.34; F, 54.38. Found:
C, 39.93; H, 2.19; N, 3.30; F, 54.43.
P en ta flu or oben zyla m in e h yd r och lor id e (10h ): 94%
1
from N-benzylidene derivative 5h ; H NMR (CD3CN/CD3OD,
3:1) δ 4.24 (t, J H-F ) 1.2 Hz); 19F NMR (CD3CN/CD3OD, 3:1)
δ -142.90 (m, 2F), -154.49 (m, 1F), -164.23 (m, 2F).
1,1,1-Tr iflu or oisopr opylam in e h ydr och lor ide (10i): 92%
1
N-Ben zylid en ep en ta flu or oben zyla m in e (5h ): Rf 0.30,
from N-benzylidene derivative 5i; H NMR (CD3CN/CD3OD,
mp 61-62 °C; 1H NMR δ 4.84 (m, 2H), 7.40-7.43 (m, 3H),
3:1) δ 1.49 (dq, 3H, J H-H ) 6.9, J H-F ) 0.6 Hz), 4.08 (dd, 1H,